Precision phenotyping, panomics, and system-level bioinformatics to delineate complex biologies of atherosclerosis: Rationale and design of the 'Genetic Loci and the Burden of Atherosclerotic Lesions' study

Autor: Aruna T. Bansal, Szilard Voros, Sarah S. Murray, G. Russell Warnick, Pál Maurovich-Horvat, Idean Marvasty, Béla Merkely, Bradley O. Brown, Gustavo Vazquez, Michael R. Barnes, Viktor Vörös
Rok vydání: 2014
Předmět:
Genetic Markers
Proteomics
Genomics
Coronary Artery Disease
Plaque imaging
Coronary Angiography
Bioinformatics
Severity of Illness Index
Coronary artery disease
Metabolomics
Lipidomics
medicine
Humans
Genetic Predisposition to Disease
Radiology
Nuclear Medicine and imaging
Prospective Studies
Vascular Calcification
Genetic Association Studies
Whole genome sequencing
medicine.diagnostic_test
business.industry
Systems Biology
Coronary Stenosis
Computational Biology
Atherosclerosis
medicine.disease
Coronary Vessels
Lipids
Plaque
Atherosclerotic
United States
Europe
Phenotype
Coronary calcium scoring
CT angiography
Genetic Loci
Research Design
Radiology Nuclear Medicine and imaging
Angiography
DNA methylation
Gene expression
Tomography
X-Ray Computed
business
Cardiology and Cardiovascular Medicine
Zdroj: Journal of Cardiovascular Computed Tomography. 8(6):442-451
ISSN: 1934-5925
0173-8828
DOI: 10.1016/j.jcct.2014.08.006
Popis: Background Complex biological networks of atherosclerosis are largely unknown. Objective The main objective of the Genetic Loci and the Burden of Atherosclerotic Lesions study is to assemble comprehensive biological networks of atherosclerosis using advanced cardiovascular imaging for phenotyping, a panomic approach to identify underlying genomic, proteomic, metabolomic, and lipidomic underpinnings, analyzed by systems biology–driven bioinformatics. Methods By design, this is a hypothesis-free unbiased discovery study collecting a large number of biologically related factors to examine biological associations between genomic, proteomic, metabolomic, lipidomic, and phenotypic factors of atherosclerosis. The Genetic Loci and the Burden of Atherosclerotic Lesions study ( NCT01738828 ) is a prospective, multicenter, international observational study of atherosclerotic coronary artery disease. Approximately 7500 patients are enrolled and undergo non–contrast-enhanced coronary calcium scanning by CT for the detection and quantification of coronary artery calcium, as well as coronary artery CT angiography for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. In addition, patients undergo whole genome sequencing, DNA methylation, whole blood–based transcriptome sequencing, unbiased proteomics based on mass spectrometry, as well as metabolomics and lipidomics on a mass spectrometry platform. The study is analyzed in 3 subsequent phases, and each phase consists of a discovery cohort and an independent validation cohort. For the primary analysis, the primary phenotype will be the presence of any atherosclerotic plaque, as detected by cardiac CT. Additional phenotypic analyses will include per patient maximal luminal stenosis defined as 50% and 70% diameter stenosis. Single-omic and multi-omic associations will be examined for each phenotype; putative biomarkers will be assessed for association, calibration, discrimination, and reclassification.
Databáze: OpenAIRE
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